Variant in PNPLA3 is associated with alcoholic liver disease

• Published in: Nature genetics Vol. 42; no. 1; pp. 21 - 23
• Main Authors: Tian, Chao, Stokowski, Renee P, Kershenobich, David, Ballinger, Dennis G, Hinds, David A
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2010; Nature Publishing Group
• Subjects: Adult; African Americans; Agriculture; Animal Genetics and Genomics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; brief-communication; Cancer Research; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Gene Frequency; Gene Function; Genetic aspects; Genetic Predisposition to Disease; Genetic Variation; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Hispanic people; Human Genetics; Humans; Lipase - genetics; Liver; Liver cirrhosis; Liver Cirrhosis, Alcoholic - genetics; Liver Diseases, Alcoholic - genetics; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Logistic Models; Male; Medical sciences; Membrane Proteins - genetics; Middle Aged; Other diseases. Semiology; Polymorphism, Single Nucleotide; Principal components analysis; Regression analysis; Risk factors; Single nucleotide polymorphisms; United States; Variant; Digestive diseases; Hepatic disease; Alcoholic hepatitis
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.488

David Hinds and colleagues report that a non-synonymous variant in PNPLA3 is associated with alcoholic liver disease and liver cirrhosis. This result follows previously reported associations of this variant with nonalcoholic fatty liver disease. Two genome-wide association studies (GWAS) have described associations of variants in PNPLA3 with nonalcoholic fatty liver and plasma liver enzyme levels. We investigated the contributions of these variants to liver disease in Mestizo subjects with a history of alcohol dependence. We found that rs738409 in PNPLA3 is strongly associated with alcoholic liver disease and clinically evident alcoholic cirrhosis (unadjusted OR= 2.25, P =1.7 × 10 −10 ; ancestry-adjusted OR=1.79, P =1.9 × 10 −5 ).